RNAscope Multiplex Fluorescent Assay

Coinfection of porcine deltacoronavirus and porcine epidemic diarrhea virus altered viral tropism in gastrointestinal tract in a piglet model

Coinfection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) is one of common findings in diarrheal piglets that cause massive economic losses to the pig industry globally. However, the mechanism of the co-infection is unclear. In this study, neonatal non-colostrum-fed piglets were exposed orally with a single infection of PDCoV or PEDV, or coinfection of PDCoV and PEDV. Clinically all viral infected piglets developed watery diarrhea and dehydration in 24 h post-exposure (hpe) and were succumbed to viral diarrhea disease and euthanized at 72 hpe.

Role of trace amine‑associated receptor 1 in the medial prefrontal cortex in chronic social stress-induced cognitive deficits in mice

Emerging evidence supports an essential role of trace amine-associated receptor 1 (TAAR1) in neuropsychiatric disorders such as depression and schizophrenia. Stressful events are critical contributors to various neuropsychiatric disorders. This study examined the role of TAAR1 in mediating the negative outcomes of stressful events. In mice that experienced chronic social defeat stress but not acute stress, a significant reduction in the TAAR1 mRNA level was found in the medial prefrontal cortex (mPFC), a brain region that is known to be vulnerable to stress experience.

RIM-Binding Proteins Are Required for Normal Sound-Encoding at Afferent Inner Hair Cell Synapses

The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 – multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and CaV1.3 – in IHC presynaptic function and hearing.

The Exon Junction Complex core factor eIF4A3 is a key regulator of HPV16 gene expression

High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas. Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In this study, we investigated the implication of the DEAD-box helicase eIF4A3, an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 upregulated E7 oncoprotein levels.

REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity

Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking1,2. The molecular mechanism that underlies this temporal pattern is unclear. Here we show that the nuclear receptors REV-ERB-α and REV-ERB-β (referred to here as 'REV-ERB') in the GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviours during regular light-dark cycles.

Japanese encephalitis virus manipulates lysosomes membrane for RNA replication and utilizes autophagy components for intracellular growth

Japanese encephalitis virus is absolutely dependent on their host cells and has evolved various strategies to manipulate the cellular secretory pathways for viral replication. However, how cellular secretory pathways are hijacked, and the origin of the viral vesicles remains elusive during JEV replication. Here we show how JEV manipulates multiple components of the cellular secretory pathway, including autophagic machinery, to generate a superior environment for genome replication.

RNASCOPE MULTIPLEX IN SITU HYBRIDIZATION: A POWERFUL COMPLEMENT FOR STUDIES OF PROTEIN-PROTEIN INTERACTIONS IN COMPLEX TISSUES.

Introduction Protein-protein interactions form the basis most physiological and pathophysiological mechanisms, but studying them at the tissue level is challenging, especially when they are transient, weak or involve low-abundance molecules in complex tissues. The problem is compounded when using antibody-based approaches, due to the paucity of rigorously validated antibodies for in situ studies.

Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos

Primary cilia are ubiquitous microtubule-based organelles that serve as signaling hubs for numerous developmental pathways, most notably the Hedgehog (Hh) pathway. Defects in the structure or function of primary cilia result in a class of diseases called ciliopathies. It is well known that primary cilia participate in transducing a Hh signal, and as such ciliopathies frequently present with phenotypes indicative of aberrant Hh function.

MFG-E8 Plays an Important Role in Attenuating Cerulein-Induced Acute Pancreatitis in Mice

Milk fat globule-EGF factor 8 (MFG-E8) is a secreted glycoprotein that regulates tissue homeostasis, possesses potent anti-inflammatory properties, and protects against tissue injury. The human pancreas expresses MFG-E8; however, the role of MFG-E8 in the pancreas remains unclear. We examined the expression of MFG-E8 in the pancreas at baseline and during cerulein-induced acute pancreatitis in mice and determined whether MFG-E8 attenuates the progression of pancreatitis, a serious inflammatory condition that can be life-threatening.

The CD33 short isoform is a gain-of-function variant that enhances Aβ1-42 phagocytosis in microglia

CD33 is genetically linked to Alzheimer's disease (AD) susceptibility through differential expression of isoforms in microglia. The role of the human CD33 short isoform (hCD33m), preferentially encoded by an AD-protective CD33 allele (rs12459419T), is unknown. Here, we test whether hCD33m represents a loss-of-function or gain-of-function variant. We have developed two models to test the role of hCD33m. The first is a new strain of transgenic mice expressing hCD33m in the microglial cell lineage.

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